This is a grant for the support of the protein structure laboratory at Caltech. The main objective of this program is an understanding of the interactions between proteins, nucleic acids, and organic intercalating molecules as they are involved in biological control. Four specific projects are covered by this grant: 1. Lactose repressor/operator crystallography; 2. Lactose repressor/operator chemistry; 3. Crystallography of small DNA molecules (4 to 10 base pairs) and their complexes with intercalating agents; 4. Prokaryotic and eukaryotic cytochrome c crystallography. Lac operator has been synthesized in this laboratory and cloned in plasmids to produce strains of E. coli that will ensure a steady supply of operator for crystal and chemical studies. The operator will be co-crystallized with repressor, and the x-ray structure analysis of their complex carried out. Physico-chemical studies of the repressor/operator interaction will be carried out in parallel, using spectroscopic and kinetic methods. DNA of planned sequences in the 4 to 10 base pair range will be synthesized and tested against a spectrum of intercalators for formation of a crystallizable intercalation complex, and the crystal structures of these complexes and of the DNA itself will be solved. In a conclusion to the cytochrome c studies, tuna ferri- and ferro-cytochrome c will be refined at 1.5 angstrom units resolution, and the structure of the four-heme cytochrome c3 from Desulfovibrio vulgaris will be solved.